{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:54:38Z","timestamp":1790711678672,"version":"4.1.0"},"reference-count":47,"publisher":"Elsevier BV","issue":"8","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["DRCRPG-100002"],"award-info":[{"award-number":["DRCRPG-100002"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["307027\/Z\/23\/Z"],"award-info":[{"award-number":["307027\/Z\/23\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203128\/Z\/16\/Z"],"award-info":[{"award-number":["203128\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["110091\/Z\/15\/Z"],"award-info":[{"award-number":["110091\/Z\/15\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"UK Research and Innovation Medical Research Council","doi-asserted-by":"publisher","award":["MR\/W031698\/1"],"award-info":[{"award-number":["MR\/W031698\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cell Reports"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1016\/j.celrep.2026.117787","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T02:27:01Z","timestamp":1785983221000},"page":"117787","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["Inhibitory TIGIT signaling is dependent on T cell receptor activation"],"prefix":"10.1016","volume":"45","author":[{"given":"William H.","family":"Zammit","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy J.","family":"Le Maistre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.E.","family":"Elliot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart A.","family":"Cain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Humphries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel M.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8242-4901","authenticated-orcid":false,"given":"Jonathan D.","family":"Worboys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.celrep.2026.117787_bib1","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.immuni.2024.01.010","article-title":"LAG-3, TIM-3, and TIGIT: Distinct functions in immune regulation","volume":"57","author":"Joller","year":"2024","journal-title":"Immunity"},{"key":"10.1016\/j.celrep.2026.117787_bib2","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/ni.1674","article-title":"The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells","volume":"10","author":"Yu","year":"2009","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.celrep.2026.117787_bib3","doi-asserted-by":"crossref","first-page":"17858","DOI":"10.1073\/pnas.0903474106","article-title":"The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity","volume":"106","author":"Stanietsky","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.celrep.2026.117787_bib4","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1002\/eji.200839116","article-title":"A novel molecular interaction for the adhesion of follicular CD4 T cells to follicular DC","volume":"39","author":"Boles","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"10.1016\/j.celrep.2026.117787_bib5","doi-asserted-by":"crossref","first-page":"3000","DOI":"10.4049\/jimmunol.1700407","article-title":"Functional Anti-TIGIT Antibodies Regulate Development of Autoimmunity and Antitumor Immunity","volume":"200","author":"Dixon","year":"2018","journal-title":"J. Immunol."},{"key":"10.1016\/j.celrep.2026.117787_bib6","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.ccell.2014.10.018","article-title":"The Immunoreceptor TIGIT Regulates Antitumor and Antiviral CD8 + T Cell Effector Function","volume":"26","author":"Johnston","year":"2014","journal-title":"Cancer Cell"},{"key":"10.1016\/j.celrep.2026.117787_bib7","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.immuni.2022.02.005","article-title":"Mechanistic convergence of the TIGIT and PD-1 inhibitory pathways necessitates co-blockade to optimize anti-tumor CD8+ T cell responses","volume":"55","author":"Banta","year":"2022","journal-title":"Immunity"},{"key":"10.1016\/j.celrep.2026.117787_bib8","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1038\/s43018-024-00870-6","article-title":"TIGIT and PD-L1 co-blockade promotes clonal expansion of multipotent, non-exhausted antitumor T cells by facilitating co-stimulation","volume":"5","author":"Nutsch","year":"2024","journal-title":"Nat. Cancer"},{"key":"10.1016\/j.celrep.2026.117787_bib9","doi-asserted-by":"crossref","first-page":"6375","DOI":"10.1158\/0008-5472.CAN-17-0381","article-title":"CD155T\/TIGIT Signaling Regulates CD8+ T-cell Metabolism and Promotes Tumor Progression in Human Gastric Cancer","volume":"77","author":"He","year":"2017","journal-title":"Cancer Res."},{"key":"10.1016\/j.celrep.2026.117787_bib10","doi-asserted-by":"crossref","first-page":"105472","DOI":"10.1016\/j.oraloncology.2021.105472","article-title":"TIGIT\/CD155 blockade enhances anti-PD-L1 therapy in head and neck squamous cell carcinoma by targeting myeloid-derived suppressor cells","volume":"121","author":"Mao","year":"2021","journal-title":"Oral Oncol."},{"key":"10.1016\/j.celrep.2026.117787_bib11","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-023-40755-3","article-title":"TIGIT can inhibit T cell activation via ligation-induced nanoclusters, independent of CD226 co-stimulation","volume":"14","author":"Worboys","year":"2023","journal-title":"Nat. Commun."},{"key":"10.1016\/j.celrep.2026.117787_bib12","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1002\/eji.201243072","article-title":"Mouse TIGIT inhibits NK-cell cytotoxicity upon interaction with PVR","volume":"43","author":"Stanietsky","year":"2013","journal-title":"Eur. J. Immunol."},{"key":"10.1016\/j.celrep.2026.117787_bib13","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1038\/cdd.2012.141","article-title":"Recruitment of Grb2 and SHIP1 by the ITT-like motif of TIGIT suppresses granule polarization and cytotoxicity of NK cells","volume":"20","author":"Liu","year":"2013","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.celrep.2026.117787_bib14","doi-asserted-by":"crossref","first-page":"17647","DOI":"10.1074\/jbc.M114.572420","article-title":"T-cell Immunoglobulin and ITIM Domain (TIGIT) Receptor\/Poliovirus Receptor (PVR) Ligand Engagement Suppresses Interferon-\u03b3 Production of Natural Killer Cells via \u03b2-Arrestin 2-mediated Negative Signaling","volume":"289","author":"Li","year":"2014","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.celrep.2026.117787_bib15","doi-asserted-by":"crossref","first-page":"3869","DOI":"10.4049\/jimmunol.1103627","article-title":"The TIGIT\/CD226 axis regulates human T cell function","volume":"188","author":"Lozano","year":"2012","journal-title":"J. Immunol."},{"key":"10.1016\/j.celrep.2026.117787_bib16","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/s41435-023-00251-6","article-title":"Do inhibitory receptors need to be proximal to stimulatory receptors to function?","volume":"25","author":"Worboys","year":"2024","journal-title":"Genes Immun."},{"key":"10.1016\/j.celrep.2026.117787_bib17","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1038\/nprot.2016.018","article-title":"Spatially resolved proteomic mapping in living cells with the engineered peroxidase APEX2","volume":"11","author":"Hung","year":"2016","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.celrep.2026.117787_bib18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00418-011-0880-5","article-title":"Coordinate-based colocalization analysis of single-molecule localization microscopy data","volume":"137","author":"Malkusch","year":"2012","journal-title":"Histochem. Cell Biol."},{"key":"10.1016\/j.celrep.2026.117787_bib19","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/S0952-7915(00)00083-2","article-title":"Signal transduction by the TCR for antigen","volume":"12","author":"Kane","year":"2000","journal-title":"Curr. Opin. Immunol."},{"key":"10.1016\/j.celrep.2026.117787_bib20","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1038\/ni1369","article-title":"The kinetic-segregation model: TCR triggering and beyond","volume":"7","author":"Davis","year":"2006","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.celrep.2026.117787_bib21","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1084\/jem.20112741","article-title":"Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2","volume":"209","author":"Yokosuka","year":"2012","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.celrep.2026.117787_bib22","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1038\/s41586-020-2851-2","article-title":"Immune receptor inhibition through enforced phosphatase recruitment","volume":"586","author":"Fernandes","year":"2020","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2026.117787_bib23","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1126\/science.aaf1292","article-title":"T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition","volume":"355","author":"Hui","year":"2017","journal-title":"Science"},{"key":"10.1016\/j.celrep.2026.117787_bib24","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/ni877","article-title":"CD45 ectodomain controls interaction with GEMs and Lck activity for optimal TCR signaling","volume":"4","author":"Irles","year":"2003","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.celrep.2026.117787_bib25","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41592-020-01010-5","article-title":"Deciphering molecular interactions by proximity labeling","volume":"18","author":"Qin","year":"2021","journal-title":"Nat. Methods"},{"key":"10.1016\/j.celrep.2026.117787_bib26","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/S1471-4906(01)01973-1","article-title":"PI 3-K and T-cell activation: limitations of T-leukemic cell lines as signaling models","volume":"22","author":"Astoul","year":"2001","journal-title":"Trends Immunol."},{"key":"10.1016\/j.celrep.2026.117787_bib27","doi-asserted-by":"crossref","first-page":"1001152","DOI":"10.1371\/journal.pbio.1001152","article-title":"Remodelling of Cortical Actin Where Lytic Granules Dock at Natural Killer Cell Immune Synapses Revealed by Super-Resolution Microscopy","volume":"9","author":"Brown","year":"2011","journal-title":"PLoS Biol."},{"key":"10.1016\/j.celrep.2026.117787_bib28","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/imr.12107","article-title":"The Central Role of the Cytoskeleton in Mechanisms and Functions of the NK Cell Immune Synapse","volume":"256","author":"Lagrue","year":"2013","journal-title":"Immunol. Rev."},{"key":"10.1016\/j.celrep.2026.117787_bib29","doi-asserted-by":"crossref","first-page":"463","DOI":"10.3390\/cells8050463","article-title":"Actin Cytoskeleton Straddling the Immunological Synapse between Cytotoxic Lymphocytes and Cancer Cells","volume":"8","author":"Wurzer","year":"2019","journal-title":"Cells"},{"key":"10.1016\/j.celrep.2026.117787_bib30","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.cub.2017.12.044","article-title":"Nanoscale Dynamism of Actin Enables Secretory Function in Cytolytic Cells","volume":"28","author":"Carisey","year":"2018","journal-title":"Curr. Biol."},{"key":"10.1016\/j.celrep.2026.117787_bib31","doi-asserted-by":"crossref","first-page":"14347","DOI":"10.1038\/ncomms14347","article-title":"Self-organizing actin patterns shape membrane architecture but not cell mechanics","volume":"8","author":"Fritzsche","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.celrep.2026.117787_bib32","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.ceb.2021.02.008","article-title":"Cytoskeletal control of the secretory immune synapse","volume":"71","author":"Douanne","year":"2021","journal-title":"Curr. Opin. Cell Biol."},{"key":"10.1016\/j.celrep.2026.117787_bib33","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/s41590-022-01394-w","article-title":"NgR1 is an NK cell inhibitory receptor that destabilizes the immunological synapse","volume":"24","author":"Oh","year":"2023","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.celrep.2026.117787_bib34","doi-asserted-by":"crossref","first-page":"eadh2456","DOI":"10.1126\/scisignal.adh2456","article-title":"PD-1 inhibits T cell actin remodeling at the immunological synapse independently of its signaling motifs","volume":"16","author":"Paillon","year":"2023","journal-title":"Sci. Signal."},{"key":"10.1016\/j.celrep.2026.117787_bib35","doi-asserted-by":"crossref","first-page":"55376","DOI":"10.1074\/jbc.M409342200","article-title":"Engaged and Bystander T Cell Receptors Are Down-modulated by Different Endocytotic Pathways","volume":"279","author":"Monjas","year":"2004","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.celrep.2026.117787_bib36","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1038\/ni855","article-title":"c-Cbl and Cbl-b regulate T cell responsiveness by promoting ligand-induced TCR down-modulation","volume":"3","author":"Naramura","year":"2002","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.celrep.2026.117787_bib37","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1126\/science.1202947","article-title":"Trans-endocytosis of CD80 and CD86: A molecular basis for the cell-extrinsic function of CTLA-4","volume":"332","author":"Qureshi","year":"2011","journal-title":"Science"},{"key":"10.1016\/j.celrep.2026.117787_bib38","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20221391","article-title":"CTLA4 depletes T cell endogenous and trogocytosed B7 ligands via cis-endocytosis","volume":"220","author":"Xu","year":"2023","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.celrep.2026.117787_bib39","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1093\/bioinformatics\/btu202","article-title":"ThunderSTORM: a comprehensive ImageJ plug-in for PALM and STORM data analysis and super-resolution imaging","volume":"30","author":"Ovesn\u00fd","year":"2014","journal-title":"Bioinformatics"},{"key":"10.1016\/j.celrep.2026.117787_bib40","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.24463","article-title":"Proteomic mapping of cytosol-facing outer mitochondrial and ER membranes in living human cells by proximity biotinylation","volume":"6","author":"Hung","year":"2017","journal-title":"eLife"},{"key":"10.1016\/j.celrep.2026.117787_bib41","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.matbio.2022.11.001","article-title":"ADAMTS6 cleaves the large latent TGF\u03b2 complex and increases the mechanotension of cells to activate TGF\u03b2","volume":"114","author":"Cain","year":"2022","journal-title":"Matrix Biol."},{"key":"10.1016\/j.celrep.2026.117787_bib42","article-title":"Manchester Proteome Profiler: A User-Friendly Platform for Quantitative Proteomic Analysis","author":"Cain","year":"2026","journal-title":"bioRxiv"},{"key":"10.1016\/j.celrep.2026.117787_bib43","doi-asserted-by":"crossref","DOI":"10.1002\/0471143030.cb2405s68","article-title":"Supported Lipid Bilayer Technology for the Study of Cellular Interfaces","volume":"68","author":"Crites","year":"2015","journal-title":"Curr. Protoc. Cell Biol."},{"key":"10.1016\/j.celrep.2026.117787_bib44","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0158884","article-title":"Optimizing Imaging Conditions for Demanding Multi-Color Super Resolution Localization Microscopy","volume":"11","author":"Nahidiazar","year":"2016","journal-title":"PLoS One"},{"key":"10.1016\/j.celrep.2026.117787_bib45","doi-asserted-by":"crossref","first-page":"D543","DOI":"10.1093\/nar\/gkae1011","article-title":"The PRIDE database at 20 years: 2025 update","volume":"53","author":"Perez-Riverol","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.celrep.2026.117787_bib46","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/0304-4157(86)90016-X","article-title":"Supported planar membranes in studies of cell-cell recognition in the immune system","volume":"864","author":"McConnell","year":"1986","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.celrep.2026.117787_bib47","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/S0092-8674(00)81608-6","article-title":"A Novel Adaptor Protein Orchestrates Receptor Patterning and Cytoskeletal Polarity in T-Cell Contacts","volume":"94","author":"Dustin","year":"1998","journal-title":"Cell"}],"container-title":["Cell Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S221112472600865X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S221112472600865X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:29:41Z","timestamp":1789705781000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S221112472600865X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":47,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["S221112472600865X"],"URL":"https:\/\/doi.org\/10.1016\/j.celrep.2026.117787","relation":{},"ISSN":["2211-1247"],"issn-type":[{"value":"2211-1247","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Inhibitory TIGIT signaling is dependent on T cell receptor activation","name":"articletitle","label":"Article Title"},{"value":"Cell Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.celrep.2026.117787","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"117787"}}